Osteoarthritis (OA), the most prevalent joint disease, is a major cause of disability worldwide. Growth hormone (GH) has been suggested to play significant roles in maintaining articular chondrocyte function and ultimately articular cartilage (AC) homeostasis. In humans, the age-associated decline in GH levels was hypothesized to play a role in the etiology of OA. We studied the impact of adult-onset isolated GH deficiency (AOiGHD) on the life span and skeletal integrity including the AC, in 23- to 30-month-old male and female mice on C57/BL6 genetic background. Reductions in GH during adulthood were associated with extended life span and reductions in body temperature in female mice only. However, end-of-life pathology revealed high levels of lymphomas in both sexes, independent of GH status. Skeletal characterization revealed increases in OA severity in AOiGHD mice, evidenced by AC degradation in both femur and tibia, and significantly increased osteophyte formation in AOiGHD females. AOiGHD males showed significant increases in the thickness of the synovial lining cell layer that was associated with increased markers of inflammation (IL-6, iNOS). Furthermore, male AOiGHD showed significant increases in matrix metalloproteinase-13 (MMP-13), p16, and β-galactosidase immunoreactivity in the AC as compared to controls, indicating increased cell senescence. In conclusion, while the life span of AOiGHD females increased, their health span was compromised by high-grade lymphomas and the development of severe OA. In contrast, AOiGHD males, which did not show extended life span, showed an overall low grade of lymphomas but exhibited significantly decreased health span, evidenced by increased OA severity.

中文翻译：

---

成年期躯体绝经对寿命和年龄引起的骨关节炎的性别二态性影响

骨关节炎 (OA) 是最普遍的关节疾病，是全世界致残的主要原因。生长激素 (GH) 已被认为在维持关节软骨细胞功能和最终关节软骨 (AC) 稳态中发挥重要作用。在人类中，假设与年龄相关的 GH 水平下降在 OA 的病因学中起作用。我们研究了成年发病的孤立性生长激素缺乏症 (AOiGHD) 对具有 C57/BL6 遗传背景的 23 至 30 个月大的雄性和雌性小鼠的寿命和骨骼完整性（包括 AC）的影响。成年期 GH 的减少仅与雌性小鼠的寿命延长和体温降低有关。然而，临终病理学显示，无论男女，淋巴瘤水平都很高，与 GH 状态无关。骨骼特征显示 AOiGHD 小鼠的 OA 严重程度增加，股骨和胫骨的 AC 退化证明了这一点，并且 AOiGHD 雌性的骨赘形成显着增加。AOiGHD 男性的滑膜衬里细胞层的厚度显着增加，这与炎症标志物（IL-6、iNOS）的增加有关。此外，与对照组相比，雄性 AOiGHD 在 AC 中的基质金属蛋白酶 13 (MMP-13)、p16 和 β-半乳糖苷酶免疫反应性显着增加，表明细胞衰老增加。总之，虽然 AOiGHD 女性的寿命增加了，但她们的健康寿命却受到高级别淋巴瘤和严重 OA 发展的影响。相比之下，没有表现出延长寿命的 AOiGHD 男性，